Vascular endothelial growth factor C enhances cervical cancer cell invasiveness via upregulation of galectin-3 protein. (June 2014)

• Record Type: Journal Article
• Authors: Liu, Junxiu; Cheng, Yang; He, Mian; Yao, Shuzhong
• Is Part Of: Gynecological endocrinology. Volume 30:Number 6(2014:Jun.)
• Page Start: 461
• Page End: 465
• Publication Date: 2014-06
• Subjects: Endocrine gynecology -- Periodicals; Generative organs, Female -- Diseases -- Periodicals; 618.1
• DOI: 10.3109/09513590.2014.898054
• Languages: English
• ISSNs: 0951-3590

Abstract

<abstract> <title>Abstract</title> <p>Vascular endothelial growth factor C (VEGF-C) promotes cervical cancer metastasis, while the detailed mechanism remains obscure. Recent evidence shows that galectin-3 (Gal-3), a glycan binding protein, interacts with the VEGF receptors and reinforces their signal transduction. In this study, we investigated the role of Gal-3 in VEGF-C-induced cervical cancer cell invasion. On cervical carcinoma cell line SiHa cells, silencing of Gal-3 expression with specific siRNA largely impaired VEGF-C-enhanced cell invasion. Treatment with VEGF-C for 12–48 h enhanced Gal-3 protein expression, which was inhibited by the addition of NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC). Moreover, the silencing of NF-κB subunit p65 expression with specific siRNA attenuated VEGF-C-enhanced Gal-3 expression, suggesting that NF-κB is the key intermediate. Under VEGF-C stimulation, an enhanced interaction between VEGF receptor-3 (VEGF-R3) and Gal-3 was found, which may possibly lead to VEGF-R3 activation since exogenous Gal-3 induced VEGF-R3 phosphorylation in a dose- and time-dependent manner. In conclusion, our findings implied that VEGF-C enhanced cervical cancer invasiveness via upregulation of Gal-3 protein through NF-κB pathway, which may shed light on potential therapeutic strategies for cervical cancer therapy.</p> </abstract>